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Trial record 19 of 46 for:    thalidomide myeloma | Recruiting, Not yet recruiting, Available Studies

STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA

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ClinicalTrials.gov Identifier: NCT03829371
Recruitment Status : Recruiting
First Posted : February 4, 2019
Last Update Posted : February 11, 2019
Sponsor:
Information provided by (Responsible Party):
Mario Boccadoro, University of Turin, Italy

Brief Summary:

Multiple myeloma (MM) is a neoplastic disease deriving from an abnormal proliferation of monoclonal plasma cells in the bone marrow. The survival of MM patients varies from less than 6 months to more than 10 years depending on the stage of disease at diagnosis and prognostic factors. Three current standard treatments are approved for elderly or younger patients with significant comorbidities not eligible for autologous stem cell transplantation (ASCT): bortezomib-melphalan-prednisone (VMP), melphalan-prednisone- thalidomide (MPT) and lenalidomide with low-dose dexamethasone (Rd).

The consistent fraction of elderly patients with cancer and co-morbidities are at increased risk of developing frailty (the emergent geriatric syndrome), as well as physical and cognitive decline, with negative effect on nutrition and lifestyle, and eventually on responsiveness to and efficacy of treatments.

A frailty scale was recently described that categorized patients with MM as fit, intermediate or frail based on age, comorbidities, and physical and cognitive functioning. The frailty score was a predictor of death, progression of the disease, toxicity and drug discontinuation.

In this project, the investigators will compare available first line standard treatments, the triplet VMP versus the doublet Rd, in an unselected population of patients ≥ 65 years affected by MM in every day clinical practice. In the last decade, many novel and expensive drugs have been approved for this disease, yet the general older population is not adequately represented in validating trials. Nevertheless, the results and treatments derived from those trials have often been applied to the older population, with a high risk to produce a negative impact on patient functional capacity and ability to carry out daily tasks, cognitive function, depression status, nutritional condition, social situation/capability to stay at home and finally affecting their quality of life (QoL) and OS. The main aim of the project is to evaluate the best initial treatment for elderly MM patients and to compare benefits, risks, QoL and costs of currently available, standard treatments according to the frailty profile.


Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Velcade Drug: Melphalan Drug: Prednisone Drug: Lenalidomide Drug: Dexamethasone Phase 4

Detailed Description:

All patients will be randomized in a 1:1 ratio to receive:

ARM A:

Bortezomib (V):

  • 1.3 mg/m2 subcutaneously on days 1, 4, 8, 11, 22, 25, 29 and 32 in cycles 1-4;
  • 1.3 mg/m2 subcutaneously on days 1, 8, 22 and 29 in cycles 5-9.

Melphalan (M):

- 9 mg/m2 orally on days 1, 2, 3 and 4 of each cycle.

Prednisone (P):

- 60 mg/m2 orally on days 1, 2, 3 and 4 of each cycle. Each cycle is to be repeated every 42 days. Duration: Maximum 9 therapy cycles can be performed. After 9 cycles, patients will be observed until progression disease or the start of a new line of therapy.

ARM B:

Lenalidomide (R):

- 25 mg orally on days 1-21 of each cycle.

Dexamethasone (d):

- 40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is a 28-day cycles. Duration: patients will receive treatment until any sign of progression or intolerance.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 350 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A RANDOMIZED, MULTICENTER, OPEN LABEL STUDY COMPARING TWO STANDARD TREATMENTS, BORTEZOMIB-MELPHALAN-PREDNISONE (VMP) VS LENALIDOMIDE-DEXAMETHASONE (Rd) IN AUTOLOGOUS STEM CELL TRANSPLANTATION (ASCT) INELIGIBLE COMMUNITY POPULATION AFFECTED BY MULTIPLE MYELOMA (MM)
Actual Study Start Date : January 3, 2019
Estimated Primary Completion Date : January 3, 2023
Estimated Study Completion Date : January 3, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ARM A

ARM A

Velcade (V):

  • 1.3 mg/m2 subcutaneously on days 1, 4, 8, 11, 22, 25, 29 and 32 in cycles 1-4;
  • 1.3 mg/m2 subcutaneously on days 1, 8, 22 and 29 from cycle 5.

Melphalan (M):

- 9 mg/m2 orally on days 1, 2 3 and 4 of each cycle.

Prednisone (P):

- 60 mg/m2 orally on days 1, 2, 3 and 4 of each cycle. Each cycle is a 42-day cycle. Duration: Maximum 9 cycles can be performed.

Drug: Velcade
Subcutaneous use

Drug: Melphalan
Oral use

Drug: Prednisone
Oral use

Experimental: ARM B

ARM B:

Lenalidomide (R):

-25 mg orally on days 1-21 of each cycle.

Dexamethasone (d):

-40 mg orally on days 1, 8, 15 and 22 of each cycle. Each cycle is a 28-day cycle. Duration: until PD or intolerance.

Drug: Lenalidomide
Oral use

Drug: Dexamethasone
Oral use




Primary Outcome Measures :
  1. Progression-free survival (PFS) [ Time Frame: 5 years ]
    Number of months from the date of randomization to the date of first observation of PD, or death from any cause as an event.


Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: 5 years ]
    Overall response rate will include complete response (CR), very good partial response (VGPR) and partial response (PR) using the International Response Criteria. Responders are defined as subjects with at least a PR.

  2. Duration of response (DOR) [ Time Frame: 5 years ]
    Time between first documentation of response and PD. Responders without disease progression will be censored either at the time of lost to FU, at the time of death due to other cause than PD, or at the end of the study.

  3. Overall survival (OS) [ Time Frame: 5 years ]
    Time between randomization and death. Subjects who die will be censored at time of death as an event, regardless cause of death.

  4. Progression-free survival 2 (PFS2) [ Time Frame: 5 years ]
    Time from randomization to objective tumor progression on next-line treatment or death from any cause.

  5. Time to next therapy (TNT) [ Time Frame: 5 years ]
    Time to next therapy will be measured from the date of randomization to the date of next anti-myeloma therapy. Death due to any cause before starting therapy will be considered an event.

  6. Time to progression (TTP) [ Time Frame: 5 years ]
    Time to progression will be measured from the date of randomization to the date of first observation of PD, or deaths related to PD.

  7. Adverse events [ Time Frame: 5 years ]
    Safety will be evaluated by assessing the incidence, severity and type of AEs according to NCI-CTCAE v. 4.0.

  8. Rate of treatment discontinuation or death for toxicity [ Time Frame: 5 years ]
    Incidence of treatment discontinuation for toxicities as well as the rate of death for toxicity will be evaluated during the entire duration of the trial (toxicities evaluated according to NCI-CTCAE v. 4.0)

  9. Frailty score [ Time Frame: 5 years ]
    Validation of Myeloma Frailty Score (fit score=0; intermediate-fitness score=1, and frail score≥2) that assess comorbidities, cognitive and physical status in real population according to geriatric assessment and considering patients' non-Myeloma polydrug therapies.

  10. Quality of Life through Health-Related QoL (HRQoL) [ Time Frame: 5 years ]
    Quality of Life will be evaluated through questionnaire: EORTC-QLQ-C30 (a generic, multidimensional, cancer-specific QoL questionnaire).

  11. Quality of Life through Health-Related QoL (HRQoL) [ Time Frame: 5 years ]
    Quality of Life will be evaluated through questionnaire for MM patients: QLQ-MY20 (a specific 20- item MM module).

  12. Quality of Life through Health-Related QoL (HRQoL) [ Time Frame: 5 years ]
    Quality of Life will be evaluated through questionnaire: EQ-5D-5L (a generic assessment of five health categories and overall health score).

  13. Direct health related costs and indirect costs [ Time Frame: 5 years ]
    Health-related costs will be reported through Questionnaires For Patients Costs Evaluation reported in the protocol evaluating working activities.

  14. Direct health related costs and indirect costs [ Time Frame: 5 years ]
    Health-related costs will be reported through Questionnaires For Patients Costs Evaluation reported in the protocol evaluating care assistance.

  15. Direct health related costs and indirect costs [ Time Frame: 5 years ]
    Health-related costs will be reported through Questionnaires For Patients Costs Evaluation reported in the protocol evaluating health care visit.

  16. Risk of infectious complications [ Time Frame: 5 years ]
    Infectious risk complications will be evaluated through a scale evaluating the number of adverse events, severity, type of infection, need for hospitalization (yes/no), number of days of suspension of study treatment. All these data will be combined in the statistical analysis to combine different outcome of treatments.



Information from the National Library of Medicine

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Ages Eligible for Study:   65 Years and older   (Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients has given voluntary written informed consent before the performance of any study related procedure;
  • Patients with newly diagnosed symptomatic multiple myeloma (NDMM) based on standard IMWG (International Myeloma Working Group) criteria:
  • Clonal bone marrow plasma cells >=10% or biopsy-proven bony or extramedullary plasmacytoma and any one or more of the following CRAB features and myeloma-defining events:
  • evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically

    • Hypercalcemia: serum calcium >0.25 mmol/L (>1mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11mg/dL)
    • Renal insufficiency: creatinine clearance (CLcr)<40 mL per minute (measured or estimated by validated equations) or serum creatinine > 177 micro mol/L (>2mg/dL)
    • Anemia: hemoglobin value of >20g/L below the lower limit of normal, or a hemoglobin value <100g/L
    • Bone lesions: one or more osteolytic lesion on skeletal radiography, CT, or PET/CT. If bone marrow has <10% clonal plasma cells, more than one bone lesion is required to distinguish from solitary plasmacytoma with minimal marrow involvement
  • Any one or more of the following biomarkers of malignancy:

    • Clonal bone marrow plasma cell percentage >=60% (clonality should be established by showing kappa/lambda-light-chain restriction on flow cytometry, immunohistochemistry, or immunofluorescence. Bone marrow plasma cell percentage should preferably be estimated from a core biopsy specimen; in case of a disparity between the aspirate and core biopsy, the highest value should be used)
    • Involved:uninvolved serum free light chain ratio >=100 (values based on the serum Freelite assay. The involved free light chain must be >=100 mg/L)
    • >1 focal lesion detected by MRI (magnetic resonance imaging) studies (each focal lesion must be 5 mm or more in size
  • According to physician's opinion, patients can undergo either one of the two standard treatments and procedures;
  • Females of childbearing potential (FBCP) must use an effective contraceptive method for 28 days before the study treatment, during the treatment and for at least 3 months after the last dose of study drugs;
  • Male subjects must use an effective barrier method if sexually active with FCBP during treatment and for at least 6 months after the last dose of study drug;
  • Patients should be ineligible for ASCT, defined as:
  • >= 65 years old
  • younger than 65 years but who reject the transplant procedure or with abnormal cardiac, pulmonary, hepatic and renal function defined as [1]:

    • LVEF (left ventricular ejection fraction) < 40%
    • FEV1 (forced expiratory volume-1 second) < 40%
    • Bilirubin > 1.5 UNL, AST/ALT >2.5 UNL Creatinine clearance < 60 mL/min.

Exclusion Criteria:

  • Hypersensitivity to any active substance or to any of the excipients (lactose, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, boron, mannitol, nitrogen, crospovidone, colloidal anhydrous silica, hypromellose, titanium dioxide, macrogol, talc, sodium starch glycolate, sodium benzoate, propylene glycol, sodium dihydrogen phosphate, hydroxypropyl beta cyclodextrin, sodium saccharin, sodium EDTA, sodium hydroxide);
  • Pregnant and lactating women;
  • FBCP that do not follow the Pregnancy Prevention Plan requirements;
  • Acute diffuse infiltrative pulmonary and pericardial disease;
  • Acute viral infections (e.g. herpes simplex or ocular herpes simplex, herpes zoster, varicella);
  • Systemic mycotic or bacterial infections, unless specific anti-infectious therapy is ongoing;
  • Peptic ulcer;
  • Psychosis;
  • Administration of prophylactic vaccine from 8 to 2 weeks before starting treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03829371


Contacts
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Contact: Mario Boccadoro, Prof. 00390116336107 clinical.trials@unito.it

Locations
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Italy
Dipartimento di Biotecnologie Molecolari e Scienze per la Salute Recruiting
Torino, TO, Italy, 10126
Contact: Mario Boccadoro, Prof.    00390116336107    clinical.trials@unito.it   
Sponsors and Collaborators
University of Turin, Italy

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Responsible Party: Mario Boccadoro, Principal Investigator, University of Turin, Italy
ClinicalTrials.gov Identifier: NCT03829371     History of Changes
Other Study ID Numbers: Real MM
First Posted: February 4, 2019    Key Record Dates
Last Update Posted: February 11, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Mario Boccadoro, University of Turin, Italy:
TRANSPLANT INELIGIBLE
STANDARD TREATMENTS

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Dexamethasone acetate
Prednisone
Lenalidomide
Melphalan
Bortezomib
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists